Selective Reminding Test Total Recall Research Articles

79 Brief Subjective Memory Screener Predicts Memory Dysfunction

Objective:Alzheimer’s disease (AD) is expected to affect over 7 million older Americans by 2025. Development of fast and inexpensive screening measures for routine screening is critical for identifying those suffering from the earliest stages of AD including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). Here we assess the validity and utility of a brief, 5-item SCD screener and its associations with neuropsychological performance as compared to an existing objective cognitive screener, the Mini Mental Status Exam (MMSE).Participants and Methods:Development: A brief, 5-item SCD questionnaire was developed based on a more extensive 20-item version previously validated (Chapman et al. 2021). Participants: 27 cognitively diverse (MCI and cognitively normal) community dwelling older adults were recruited for this study. Mean age: 71.9 ± 7. Inclusion criteria include memory concerns. Exclusion criteria include no previous diagnoses of neurodegenerative diseases and/or major stroke. Administration: Participants completed a brief, 5-item SCD screener along with cognitive testing including the MMSE and a clinically validated list-learning test, the Selective Reminding Test (SRT). Statistical Methods: Spearman 2-tailed correlations were conducted to assess the relationship between the two screening measures, and their relationships to the SRT. Outcome measures on the SRT included total recall (max: 72) and delayed recall (max: 12). All cognitive measures were demographically adjusted with normative data.Results:The mean total for the SCD screener was 2.1 ±1.1, and the mean MMSE score was 29.2 ± 1.2. The SCD screener was associated with MMSE scores (r= -.39, p= .043), SRT Total Recall (r= -.43, p= .024) and Delayed Recall (r=-.42, p=.031) measures. MMSE scores did not associate with either SRT outcome (p>.05).Conclusions:Results support the utility and validity of a brief subjective cognitive decline screener for identifying those who may be experiencing memory dysfunction. The brief SCD screener outperformed the MMSE, an existing and widely used objective screening measure. Associations between the SCD screener and SRT outcomes support the validity and utility of the brief screener and recapitulate previous findings with the more extensive version of the SCD questionnaire (Chapman et al. 2021). Ongoing research is focusing on the utility of the screener in frontline clinical settings and translation of the screener into Spanish.

Association of Emerging β-Amyloid and Tau Pathology With Early Cognitive Changes in Clinically Normal Older Adults.

Alzheimer disease (AD) clinical trials are moving earlier in the disease process according to emerging signs of β-amyloid (Aβ) and tau pathology. If early treatment is the right time for intervention, it is critical to find the right test to optimize cognitive outcome measures for clinical trials. We sought to identify cognitive measures associated with the earliest detectable signs of emerging Aβ and tau pathology. One hundred twelve clinically normal adults with longitudinal Pittsburgh compound B (PiB)-PET, 18F-flortaucipir (FTP)-PET, and cognitive data for ≥7 years were included from the Harvard Aging Brain Study (HABS). Analyses assessed those initially classified as PiB- (less than Centiloid [CL] 20) and then expanded to include PiB+ individuals up to CL40, the approximate threshold beyond which neocortical tau proliferation begins. Separate linear mixed-effects models assessed the effects of emerging global Aβ (PiB slope) and tau (baseline FTP level and FTP slope) in the entorhinal and inferior temporal (IT) cortices on multiple cognitive tasks and the Preclinical Alzheimer's Cognitive Composite (PACC) over time. Steeper PiB slopes were associated with declining processing speed (Digit Symbol Substitution Test [DSST], Trail Making Test Part A) in those <CL20 and expanded to include learning/memory retrieval (FCSRT-FR], Selective Reminding Test Total Recall [SRT-tr], Logical Memory Immediate Recall) in the <CL40 group. FTP had limited effects under CL20, with only rising right IT FTP slope related to declining FCSRT-FR and SRT-tr learning/memory retrieval. When we expanded to include those initially <CL40, rising FTP level or slope was related to declines across all tasks, and PiB slope effects on memory retrieval but not DSST score were reduced. A composite measure of processing speed and memory retrieval tasks provided the strongest prediction of decline under CL40, while PACC score remained optimal at high levels of Aβ (>CL40). Early, Aβ-mediated cognitive slowing was detected for processing speed measures, while early memory retrieval declines were associated with emerging Aβ and tau pathology. Composites of these measures may help determine whether anti-Aβ or anti-tau therapies administered at the first signs of pathology might preserve cognitive function. This study provides Class I evidence that in clinically normal older adults, emerging PET-detected AD pathology is associated with declining processing speeds and memory retrieval.

PLACEBO-CONTROLLED TRIAL OF DONEPEZIL FOLLOWING ANTIDEPRESSANT TREATMENT IN PATIENTS WITH COMORBID DEPRESSION AND COGNITIVE IMPAIRMENT

In patients with comorbid depression and cognitive impairment, antidepressants are commonly used but the utility of cholinesterase inhibitors (CheI) as cognitive enhancers is not established. Eighty elderly (55–95 years old) depressed, cognitively impaired (DEP-CI) patients participated in the DOTCODE study at two sites: Columbia and Duke University Medical Centers. 40 of 79 patients who received antidepressant medication in the initial phase met criteria for amnestic mild cognitive impairment (MCI). After 16 weeks of open-label antidepressant treatment with antidepressants, primarily citalopram or venlafaxine, 61 patients were randomized to receive 62 weeks of the CheI donepezil 5–10 mg daily or placebo in a randomized, double-blind trial. Linear mixed effects models with random subject-specific intercepts were used to model ADAS-Cog13 and Selective Reminding Test (SRT) Total Immediate Recall over the course of the study. All models include baseline value of the outcome, age, study site, treatment, visit week, and the interaction between treatment and visit week (and interaction terms to test for moderators). In the first 16 weeks, depression improved in most patients and 39 of 61 randomized patients (64%) met responder criteria. In the 61 randomized patients, donepezil did not differ from placebo in change in the co-primary measures of ADAS-Cog13 (F=0.18, p=0.83) and SRT total recall (F=0.06, p=0.9). Four patients were diagnosed with probable Alzheimer's disease by end-trial. Apolipoprotein E e4 allele and MRI hippocampal volume were unrelated to differences in outcomes between donepezil and placebo. Periventricular hyperintensities (PVH) did not distinguish changes in cognition on donepezil from placebo on ADAS-Cog13 (F1,39 = 0.14, p = 0.71) but did on SRT total recall (F1,39 = 4.23, p = 0.04); less PVH was associated with greater improvement with donepezil on SRT total recall. In patients with comorbid depression and cognitive impairment, the addition of donepezil following antidepressant medication treatment did not improve cognition compared to placebo, though donepezil treatment was associated with better cognition in patients with less cerebrovascular disease. The findings add to those from studies in mild cognitive impairment without depression that have not demonstrated superiority for CheI over placebo in improving cognition.

Glycemia, Diabetes Status, and Cognition in Hispanic Adults Aged 55-64 Years.

To examine the association of glycemia and diabetes status with cognition among 600 Hispanics aged 55 to 64 years from Northern Manhattan. Diabetes was ascertained by history or hemoglobin A1c. Normal glucose tolerance and prediabetes were ascertained with hemoglobin A1c. Memory was assessed with the Selective Reminding Test. Executive abilities were assessed using the Color Trails 1 and 2 and verbal fluency test. The cross-sectional association of glycemia and diabetes status with cognitive performance was examined using linear regression. Participants had a mean age of 59.2 (2.9) years, 76.7% were women, and more than 65% had prediabetes or diabetes. HbA1C (β = -0.97, p < .001) and diabetes (β = -2.06, p = .001) were related with lower Selective Reminding Test total recall after adjustment for demographics, education, and vascular risk factors. Prediabetes was associated with worse performance in Color Trail 2 (β = -6.45 p = .022) after full adjustment. Higher glycemia and diabetes are related to worse memory and executive abilities in late middle age, whereas prediabetes is related only to worse executive abilities. Longitudinal follow-up is needed to understand the order and progression of these deficits.

Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort

Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of -0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation.

Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance

Although multivariate analytic techniques might identify diagnostic patterns that are not captured by univariate methods, they have rarely been used to study the neural correlates of Alzheimer's disease (AD) or cognitive impairment. Nonquantitative H 2 15O PET scans were acquired during rest in 17 probable AD subjects selected for mild severity [mean-modified Mini Mental Status Examination (mMMS) 46/57; SD 5.1], 16 control subjects (mMMS 54; SD 2.5) and 23 subjects with minimal to mild cognitive impairment but no dementia (mMMS 53; SD 2.8). Expert clinical reading had low success in discriminating AD and controls. There were no significant mean flow differences among groups in traditional univariate SPM Noxel-wise analyses or region of interest (ROI) analyses. A covariance pattern was identified whose mean expression was significantly higher in the AD as compared to controls ( P = 0.03; sensitivity 76–94%; specificity 63–81%). Sites of increased concomitant flow included insula, cuneus, pulvinar, lingual, fusiform, superior occipital and parahippocampal gyri, whereas decreased concomitant flow was found in cingulate, inferior parietal lobule, middle and inferior frontal, supramarginal and precentral gyri. The covariance analysis-derived pattern was then prospectively applied to the cognitively impaired subjects: as compared to subjects with Clinical Dementia Rating (CDR) = 0, subjects with CDR = 0.5 had significantly higher mean covariance pattern expression ( P = 0.009). Expression of this pattern correlated inversely with Selective Reminding Test total recall ( r = −0.401, P = 0.002), delayed recall ( r = −0.351, P = 0.008) and mMMS scores ( r = −0.401, P = 0.002) in all three groups combined. We conclude that patients with AD may differentially express resting cerebral blood flow covariance patterns even at very early disease stages. Significant alterations in expression of resting flow covariance patterns occur even for subjects with cognitive impairment. Expression of covariance patterns correlates with cognitive and functional performance measures, holding promise for meaningful associations with underlying biopathological processes.

P3-091 Regional distribution of white matter changes in Alzheimer's disease

P3-091 Regional distribution of white matter changes in Alzheimer's disease

Identification of Drug-Related Cognitive Impairment in Older Individuals: Challenge Studies With Diphenhydramine

The authors tested the use of repeated cognitive measures to identify those older individuals who experience cognitive decline after administration of a centrally acting medication. Subjects were 30 medically stable, older volunteers, mean age 71.4. Administration was a double-blind, placebo-controlled, crossover "challenge" from baseline to placebo, 50 mg, or 75 mg of diphenhydramine. More patients exhibited significant cognitive decrements after 75 mg of diphenhydramine than after placebo on the Buschke Selective Reminding Test Total Recall and the Trails B test. Data were consistent with models based on prediction intervals. Quantitative algorithms using prediction equations can characterize the normal limits of within-subject variability and define excessive cognitive change in elderly subjects, showing promise for use in monitoring patients to identify those who experience mild cognitive toxicity from prescribed medications.